The overall objective of this research is to develop methods for estimating efficacy and effectiveness in the field and for characterizing complex and long-term properties of vaccines in individuals and populations. The specific aims are: (1) To develop methods for community trials of vaccines that estimate the indirect, total, and overall effects of vaccination strategies as well as the direct protective effects of vaccination, VE/S. (2) To continue development of methods for evaluating the vaccine efficacy for infectiousness, VE/1. In particular, we will develop the augmented vaccine trial design for acute and directly transmitted infectious diseases. (3) To develop methods for using exposure to infection data that may available on some individuals to improve estimation of vaccine efficacy for susceptibility, VE/5. (4) To develop designs and methods of analysis for using validation samples to correct for misclassified outcomes in vaccine studies. The goal is improved estimates of vaccine efficacy and of indirect, total, and overall effectiveness of vaccination strategies as well as designs for efficient, cost-effective studies. (5) To explore interpretation of the protective effects of vaccination, VE/5, when combining results across studies in different populations, taking into account different levels of baseline transmission and pre- existing immunity. Statistical approaches include likelihood inference, generalized estimating equations, semi-parametric methods for missing and mismeasured data, hierarchical models, and survival methods. The methods are motivated by studies of vaccines against influenza, cholera, rotavirus and tuberculosis, as well as other acute and childhood diseases.